Cytokines and the risk of preterm delivery in twin pregnancies

Line Rode; Katharina Klein; Helle Larsen; Anni Holmskov; Kirsten Riis Andreasen; Niels Uldbjerg; Jan Ramb; Birgit Bødker; Lillian Skibsted; Lene Sperling; Stefan Hinterberger; Lone Krebs; Helle Zingenberg; Eva-Christine Weiss; Isolde Strobl; Lone Laursen; Jeanette Tranberg Christensen; Kristin Skogstrand; David Michael Hougaard; Elisabeth Krampl-Bettelheim; Susanne Rosthøj; Ida Vogel; Ann Tabor

doi:10.1097/aog.0b013e31825bc3cd

Cytokines and the risk of preterm delivery in twin pregnancies

Line Rode, Katharina Klein, Helle Larsen, Anni Holmskov, Kirsten Riis Andreasen, Niels Uldbjerg, Jan Ramb, Birgit Bødker, Lillian Skibsted, Lene Sperling, Stefan Hinterberger, Lone Krebs, Helle Zingenberg, Eva-Christine Weiss, Isolde Strobl, Lone Laursen, Jeanette Tranberg Christensen, Kristin Skogstrand, David Michael Hougaard, Elisabeth Krampl-BettelheimSusanne Rosthøj, Ida Vogel, Ann Tabor

14 Citations (Scopus)

Abstract

To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels. EudraCT, , 2006-000503-41, and ClinicalTrials.gov.

Original language	English
Journal	Obstetrics and Gynecology International
Volume	120
Issue number	1
Pages (from-to)	60-68
Number of pages	9
ISSN	1687-9589
DOIs	https://doi.org/10.1097/aog.0b013e31825bc3cd
Publication status	Published - Jul 2012

Keywords

Adult
Cytokines
Dried Blood Spot Testing
Female
Humans
Interleukin-8
Pregnancy
Pregnancy, Twin
Premature Birth
Progesterone

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10.1097/aog.0b013e31825bc3cd

Cite this

Rode, L., Klein, K., Larsen, H., Holmskov, A., Andreasen, K. R., Uldbjerg, N., Ramb, J., Bødker, B., Skibsted, L., Sperling, L., Hinterberger, S., Krebs, L., Zingenberg, H., Weiss, E.-C., Strobl, I., Laursen, L., Christensen, J. T., Skogstrand, K., Hougaard, D. M., ... Tabor, A. (2012). Cytokines and the risk of preterm delivery in twin pregnancies. Obstetrics and Gynecology International, 120(1), 60-68. https://doi.org/10.1097/aog.0b013e31825bc3cd

Rode, L, Klein, K, Larsen, H, Holmskov, A, Andreasen, KR, Uldbjerg, N, Ramb, J, Bødker, B, Skibsted, L, Sperling, L, Hinterberger, S, Krebs, L , Zingenberg, H, Weiss, E-C, Strobl, I, Laursen, L, Christensen, JT, Skogstrand, K, Hougaard, DM, Krampl-Bettelheim, E, Rosthøj, S, Vogel, I & Tabor, A 2012, 'Cytokines and the risk of preterm delivery in twin pregnancies', Obstetrics and Gynecology International, vol. 120, no. 1, pp. 60-68. https://doi.org/10.1097/aog.0b013e31825bc3cd

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abstract = "To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels. EudraCT, , 2006-000503-41, and ClinicalTrials.gov.",

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T1 - Cytokines and the risk of preterm delivery in twin pregnancies

AU - Rode, Line

AU - Klein, Katharina

AU - Larsen, Helle

AU - Holmskov, Anni

AU - Andreasen, Kirsten Riis

AU - Uldbjerg, Niels

AU - Ramb, Jan

AU - Bødker, Birgit

AU - Skibsted, Lillian

AU - Sperling, Lene

AU - Hinterberger, Stefan

AU - Krebs, Lone

AU - Zingenberg, Helle

AU - Weiss, Eva-Christine

AU - Strobl, Isolde

AU - Laursen, Lone

AU - Christensen, Jeanette Tranberg

AU - Skogstrand, Kristin

AU - Hougaard, David Michael

AU - Krampl-Bettelheim, Elisabeth

AU - Rosthøj, Susanne

AU - Vogel, Ida

AU - Tabor, Ann

PY - 2012/7

Y1 - 2012/7

N2 - To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels. EudraCT, , 2006-000503-41, and ClinicalTrials.gov.

AB - To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels. EudraCT, , 2006-000503-41, and ClinicalTrials.gov.

KW - Adult

KW - Cytokines

KW - Dried Blood Spot Testing

KW - Female

KW - Humans

KW - Interleukin-8

KW - Pregnancy

KW - Pregnancy, Twin

KW - Premature Birth

KW - Progesterone

U2 - 10.1097/aog.0b013e31825bc3cd

DO - 10.1097/aog.0b013e31825bc3cd

M3 - Journal article

C2 - 22914392

SN - 1687-9589

VL - 120

SP - 60

EP - 68

JO - Obstetrics and Gynecology International

JF - Obstetrics and Gynecology International

IS - 1

ER -

Cytokines and the risk of preterm delivery in twin pregnancies

Abstract

Keywords

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